Open source software toolchain for automated non-targeted screening for toxins in alternative foods.

Previous published methods for non-targeted screening of toxins in alternative foods such as leaf concentrate, agricultural residues or plastic fed to biological consortia are time consuming and expensive and thus present accessibility, as well as, time-constraint issues for scientists from under resourced settings to identify safe alternative foods. The novel methodology presented here, utilizes a completely free and open source software toolchain for automatically screening unknown alternative foods for toxicity using experimental data from ultra-high-pressure liquid chromatography and mass spectrometry. The process uses three distinct tools (mass spectrometry analysis with MZmine 2, formula assignment with MFAssignR, and data filtering with ToxAssign) enabling it to be modular and easily upgradable in the future. MZmine 2 and MFAssignR have been previously described, while ToxAssign was developed here to match the formulas output by formula assignment to potentially toxic compounds in a local table, then look up toxic data on the Open Food Tox Database for the matched compounds. This process is designed to fill the gap between food safety analysis techniques and developing alternative food production techniques to allow for new methods of food production to be preliminarily tested before animal testing. The methodology was validated against a previous method using proprietary commercial software. The new process identifies all of the toxic elements the previous process identified with more detailed information than the previous process was able to provide automatically.•Efficient analysis to find potentially toxic compounds in alternative foods and resilient foods.•Identification of potentially unsafe products without the use of live animal testing.•Modular free and open source design to allow for upgrading or fitting of user needs.

Heterotopia in Individuals with 22q11.2 Deletion Syndrome.

BACKGROUND AND PURPOSE: MR imaging studies and neuropathologic findings in individuals with 22q11.2 deletion syndrome show anomalous early brain development. We aimed to retrospectively evaluate cerebral abnormalities, focusing on gray matter heterotopia, and to correlate these with subjects' neuropsychiatric impairments. MATERIALS AND METHODS: Three raters assessed gray matter heterotopia and other morphologic brain abnormalities on 3D T1WI and T2*WI in 75 individuals with 22q11.2 deletion syndrome (27 females, 15.5 [SD, 7.4] years of age) and 53 controls (24 females, 12.6 [SD, 4.7] years of age). We examined the association among the groups' most frequent morphologic findings, general cognitive performance, and comorbid neuropsychiatric conditions. RESULTS: Heterotopia in the white matter were the most frequent finding in individuals with 22q11.2 deletion syndrome (n = 29; controls, n = 0; between-group difference, P < .001), followed by cavum septi pellucidi and/or vergae (n = 20; controls, n = 0; P < .001), periventricular cysts (n = 10; controls, n = 0; P = .007), periventricular nodular heterotopia (n = 10; controls, n = 0; P = .007), and polymicrogyria (n = 3; controls, n = 0; P = .3). However, individuals with these morphologic brain abnormalities did not differ significantly from those without them in terms of general cognitive functioning and psychiatric comorbidities. CONCLUSIONS: Taken together, our findings, periventricular nodular heterotopia or heterotopia in the white matter (possibly related to interrupted Arc cells migration), persistent cavum septi pellucidi and/or vergae, and formation of periventricular cysts, give clues to the brain development disorder induced by the 22q11.2 deletion syndrome. There was no evidence that these morphologic findings were associated with differences in psychiatric or cognitive presentation of the 22q11.2 deletion syndrome.

Fast Na ion transport triggered by rapid ion exchange on local length scales.

The realization of green and economically friendly energy storage systems needs materials with outstanding properties. Future batteries based on Na as an abundant element take advantage of non-flammable ceramic electrolytes with very high conductivities. Na3Zr2(SiO4)2PO4-type superionic conductors are expected to pave the way for inherently safe and sustainable all-solid-state batteries. So far, only little information has been extracted from spectroscopic measurements to clarify the origins of fast ionic hopping on the atomic length scale. Here we combined broadband conductivity spectroscopy and nuclear magnetic resonance (NMR) relaxation to study Na ion dynamics from the µm to the angstrom length scale. Spin-lattice relaxation NMR revealed a very fast Na ion exchange process in Na3.4Sc0.4Zr1.6(SiO4)2PO4 that is characterized by an unprecedentedly high self-diffusion coefficient of 9 × 10-12 m2s-1 at -10 °C. Thus, well below ambient temperature the Na ions have access to elementary diffusion processes with a mean residence time τNMR of only 2 ns. The underlying asymmetric diffusion-induced NMR rate peak and the corresponding conductivity isotherms measured in the MHz range reveal correlated ionic motion. Obviously, local but extremely rapid Na+ jumps, involving especially the transition sites in Sc-NZSP, trigger long-range ion transport and push ionic conductivity up to 2 mS/cm at room temperature.

Mode locking in a tapered two-section quantum dot laser: design and experiment.

In this Letter, the pulse generation and pulse train stability of a tapered two-section InAs/InGaAs quantum dot laser emitting at 1250 nm are numerically predicted and experimentally verified. Simulations based on a multi-section delayed differential equation model are used to properly design a laser source able to generate stable mode-locked pulses at a 15 GHz repetition rate with picosecond width and output power larger than 1 W, and to identify the device stability regions depending on the bias conditions. Possible instabilities are associated with the existence of a leading or trailing edge net gain window outside the optical pulse. Experimentally, we confirm the existence of different stability regions where instabilities manifest in broadband or multi-periodic pulse train amplitude modulations. Our results confirm the correctness to the design and may be helpful in achieving high-power pulses while avoiding detrimental pulse train instabilities, both being important for time-critical applications.

Rapid Li Ion Dynamics in the Interfacial Regions of Nanocrystalline Solids.

Diffusive processes are ubiquitous in nature. In solid state physics, metallurgy and materials science the diffusivity of ions govern the functionality of many devices such as sensors or batteries. Motional processes on surfaces, across interfaces or through membranes can be quite different to that in the bulk. A direct, quantitative description of such local diffusion processes is, however, rare. Here, we took advantage of 7Li longitudinal nuclear magnetic relaxation to study, on the atomic length scale, the diffusive motion of lithium spins in the interfacial regions of nanocrystalline, orthorhombic LiBH4. Magnetization transients and free induction decays revealed a fast subset of Li ions having access to surface pathways that offer activation barriers (0.18 eV) much lower than those in the crystalline bulk regions (0.55 eV). These observations make orthorhombic borohydride a new nanostructured model system to study disorder-induced enhancements in interfacial diffusion processes.

Intensity noise behavior of an InAs/InGaAs quantum dot laser emitting on ground states and excited states.

We experimentally and numerically study the amplitude stability of an InAs/InGaAs quantum dot laser emitting simultaneously on ground states (GSs) and excited state (ESs) at center wavelengths of 1245 and 1168 nm, respectively. The stability is quantified by a spectrally resolved noise current analysis that is dependent on the laser injection current. We find a non-monotonic behavior of the amplitude noise which shows a reduction of up to 4 dB when the GS and ES emit simultaneously. Simulations based on a rate equation model confirm the reduction in noise and suggest the cascaded GS and ES carrier paths as the relevant underlying mechanism.

Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using (14C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

Experimental demonstration of change of dynamical properties of a passively mode-locked semiconductor laser subject to dual optical feedback by dual full delay-range tuning.

In this contribution we experimentally demonstrate the change and improvement of dynamical properties of a passively mode-locked semiconductor laser subject to optical feedback from two external cavities by coupling the feedback pulses back into the gain segment. Hereby, we tune the full delay-phase of the pulse-to-pulse period of both external cavities separately and demonstrate the change of the repetition rate, timing jitter, multi-pulse formation and side-band suppression for the first time for such a dual feedback configuration. In addition, we thereby confirm modeling predictions by achieving both a good qualitative and quantitative agreement of experimental and simulated results. Our findings suggest a path towards the realization of side-band free all-optical photonic oscillators based on mode-locked lasers.

Introduction of embryonic stem cells into vein grafts reduces intimal hyperplasia in mice.

AIM: Atherosclerosis with its cardiovascular events including cardiac and peripheral ischemia represents the main cause of death in the developed countries. Although interventional treatments like percutaneous transluminal angioplasty or stents are increasingly applied for the treatment of peripheral arterial disease, they are not always technically applicable or durable and bypass surgery is needed. Compared to synthetic grafts, vein grafts show a better patency especially when used for the lower leg as well as a lower risk for infection compared to synthetic grafts. Still the long-term patency rates are unsatisfactory due to accelerated intimal hyperplasia, a thickening of the vessel wall. The aim of this study was to elucidate, if the implantation of embryonic stem cells into vein grafts can reduce the development of intimal hyperplasia in a mouse in vivo model. METHODS: In this study we implanted LacZ-tagged (ROSA26) murine embryonic stem cells into decellularized vein grafts. Control groups were: 1) untreated veins; 2) decellularized veins; 3) decellularized veins with gel and plastic film; and 4) decellularized veins with smooth muscle cells in gel surrounded by plastic film. Six weeks after insertion into the carotid artery of mice, the grafts were excised and analyzed immunohistochemically, morphologically, and by x-gal staining and compared to the control groups. The Mann-Whitney U test was used to compare groups. Statistical significance was indicated by a value of P<0.05. RESULTS: Decellularized veins with implanted stem cells showed significantly less intimal thickening compared to all control groups (intimal hyperplasia vs. luminal circumference mean±SD 7.3±3.5 µm, median 8 µm). The control groups: 1) untreated veins (60.3±25.5 µm, median 58.5 µm); 2) decellularized veins (53.9±22.4 µm, median 48.4 µm); 3) decellularized veins with gel and plastic film (70.6±22.4 µm, median 72.6 µm); and 4) decellularized veins with smooth muscle cells in gel surrounded by plastic film (73.5±18.1 µm, median 73.6 µm) all showed the same high degree of intimal hyperplasia. CONCLUSION: This study demonstrates that embryonic stem cells have a therapeutic competence to favourably modulate intimal hyperplasia in vivo.

Enhanced minority carrier lifetimes in GaAs/AlGaAs core-shell nanowires through shell growth optimization.

The effects of AlGaAs shell thickness and growth time on the minority carrier lifetime in the GaAs core of GaAs/AlGaAs core-shell nanowires grown by metal-organic chemical vapor deposition are investigated. The carrier lifetime increases with increasing AlGaAs shell thickness up to a certain value as a result of reducing tunneling probability of carriers through the AlGaAs shell, beyond which the carrier lifetime reduces due to the diffusion of Ga-Al and/or impurities across the GaAs/AlGaAs heterointerface. Interdiffusion at the heterointerface is observed directly using high-angle annular dark field scanning transmission electron microscopy. We achieve room temperature minority carrier lifetimes of 1.9 ns by optimizing the shell growth with the intention of reducing the effect of interdiffusion.

Strain accommodation in Ga-assisted GaAs nanowires grown on silicon (111).

We study the mechanism of lattice parameter accommodation and the structure of GaAs nanowires (NWs) grown on Si(111) substrates using the Ga-assisted growth mode in molecular beam epitaxy. These nanowires grow preferentially in the zincblende structure, but contain inclusions of wurtzite at the base. By means of grazing incidence x-ray diffraction and high-resolution transmission electron microscopy of the NW-substrate interface, we show that the lattice mismatch between the NW and the substrate is released immediately after the beginning of NW growth through the inclusion of misfit dislocations, and no pseudomorphic growth is obtained for NW diameters down to 10 nm. NWs with a diameter above 100 nm exhibit a rough interface towards the substrate, preventing complete plastic relaxation. Consequently, these NWs exhibit a residual compressive strain at their bottom. In contrast, NWs with a diameter of 50 nm and below are completely relaxed because the interface is smooth.

Early recipient chimerism testing in the T- and NK-cell lineages for risk assessment of graft rejection in pediatric patients undergoing allogeneic stem cell transplantation.

Timely diagnosis of impending graft rejection is crucial for effective therapeutic intervention after allogeneic hematopoietic stem cell transplantation (SCT). We have investigated the predictive potential of early leukocyte subset-specific chimerism for graft loss in children undergoing SCT. In total, 192 pediatric patients transplanted for the treatment of malignant and non-malignant diseases after reduced-intensity or myeloablative conditioning were investigated. Surveillance of lineage-specific chimerism was initiated upon first appearance of leukocyte counts amenable to cell sorting. Graft rejection occurred in 23 patients between 24 and 492 days post-transplant (median 63 days). The first chimerism analysis of T and NK cells performed at a median of 20 days after SCT identified three different risk groups that were independent from the conditioning regimen: recipient chimerism (RC) levels in T cells below 50% indicated a very low risk of rejection (1.4%), whereas high levels of RC (>90%) both in T and NK cells heralded graft loss in the majority of patients (90%) despite therapeutic interventions. RC >50% in T cells and ≤90% in NK cells defined an intermediate-risk group in which timely immunotherapy frequently prevented rejection. Early assessment of T- and NK-cell chimerism can therefore be instrumental in the risk assessment and therapeutic management of imminent graft rejection.

Acoustically driven photon antibunching in nanowires.

The oscillating piezoelectric field of a surface acoustic wave (SAW) is employed to transport photoexcited carriers, as well as to spatially control exciton recombination in GaAs-based nanowires (NWs) on a subns time scale. The experiments are carried out in core-shell NWs transferred to a SAW delay line on a LiNbO(3) crystal. Carriers generated in the NW by a focused laser spot are acoustically transferred to a second location, leading to the remote emission of subns light pulses synchronized with the SAW phase. The dynamics of the carrier transport, investigated using spatially and time-resolved photoluminescence, is well-reproduced by computer simulations. The high-frequency contactless manipulation of carriers by SAWs opens new perspectives for applications of NWs in opto-electronic devices operating at gigahertz frequencies. The potential of this approach is demonstrated by the realization of a high-frequency source of antibunched photons based on the acoustic transport of electrons and holes in (In,Ga)As NWs.

Photodynamic therapy reduces intimal hyperplasia in prosthetic vascular bypass grafts in a pig model.

BACKGROUND: Bypass surgery has a failing frequency of 30% during the first year, mainly due to intimal hyperplasia (IH). This negative effect is most pronounced in artificial grafts. Photodynamic therapy (PDT) is a technique in which light activates photosensitizer dyes to produce free-radicals resulting in an eradication of cells in the vascular wall. The aim of this study was to determine the effectiveness of PDT to reduce IH in a preclinical porcine PTFE bypass model. MATERIAL AND METHODS: Ten pigs were used. After a pilot PDT dosimetry study (n=3) PTFE grafts were bilaterally placed into the circulation as bypasses from the common to the external iliac arteries (n=7). The right sides served as controls (C). Before implantation of the left grafts, the arterial connecting sites of the left distal anastomoses were PDT-treated. The arteries were pressurized at 180 mmHg for 5 minutes with the photosensitizer Methylene Blue (330 microg/ml), and thereafter endoluminally irradiated with laser light (lambda = 660 nm, 100 mW/cm(2), 150 J/cm(2)). After 4 weeks the specimens were retrieved and formalin fixed. Cross sections through the midportions of the distal anastomoses and the grafts were used for histology, immunohistochemistry to identify inflammatory cells and morphometric evaluation (n=7). RESULTS: No systemic side effects and no graft occlusions were noted. PDT-treated anastomoses showed reduced IH in the mid-portions of the anastomoses (Area of IH: microm(2)/microm graft: C: 6970+/-1536, PDT: 2734+/-2560; P<0.005) as well as in the grafts (C: 5391+/-4031, PDT: 777+/-1331; P<0.02). The number of inflammatory cells per microscopic field was increased after PDT (C: 24+/-16, PDT: 37+/-15; P<0.009). CONCLUSIONS: Adjuvant PDT, performed in an endovascular fashion, was a safe method to reduce prosthetic graftstenosis in a preclinical setting. This study underscores the clinical potential of PDT to inhibit the development of clinical bypass graftstenosis.

Modulation of human adventitial fibroblast function by photodynamic therapy of collagen matrix.

OBJECTIVES: Photodynamic therapy (PDT) is a promising strategy to limit restenosis. PDT depletes the resident cells from the vessel wall without adventitial cell ingrowth. This study was undertaken to further explore the mechanisms by which PDT of matrix acts on key mechanisms in the development of restenosis. MATERIALS AND METHODS: Control and PDT-treated collagen type-I matrix gels were prepared. Thereafter, untreated human fibroblasts were seeded on matrix gels (n=12). Fibroblast proliferation and invasive migration were quantified by calibrated phase contrast microscopy. Fibroblast bFGF and TGF-beta1 mRNA expression were analyzed using a quantitative real-time reverse transcription polymerase chain reaction. RESULTS: Fibroblast proliferation on PDT-treated matrix gels was reduced by 30 and 76% after 3 and 7 days, respectively (3 days: P

Relationship between clinical and echocardiography-derived parameters and atrial activation as measured by the P-wave signal-averaged electrocardiogram.

UNLABELLED: P-wave signal averaging is used in an attempt to detect patients at risk of atrial arrhythmias, particularly atrial fibrillation. Although many studies utilized this method, data on the relationship between clinical and echocardiographic variables and signal averaged P-wave parameters are sparse. Thus, we performed a prospective study to evaluate the influence of important clinical and echocardiographic variables on P-wave parameters. The study included 100 probands without demonstrable cardiac disease. P-wave signal averaging was performed after echocardiographic examination in all subjects. Overall P-wave duration averaged 122 +/- 16 ms and correlated significantly with age, left atrial and left ventricular end-diastolic diameter on univariate analysis (r = 0.287, 0.393 and 0.375; p = 0.004, < 0.0001 and < 0.0001, respectively). On multivariate analysis, however, age was the only independent factor affecting signal averaged P-wave duration (p = 0.02). There were statistically significant differences in left atrial size and P-wave duration if probands were grouped according to their age. CONCLUSION: There is a significant relationship between signal averaged P-wave duration and age. This may be due to increased atrial fibrosis in elderly subjects. These data should be considered when signal-averaged P wave duration is used as a risk stratifier in patients prone to atrial fibrillation.

Tumor necrosis factor antagonism with etanercept improves systemic endothelial vasoreactivity in patients with advanced heart failure.

BACKGROUND: Anti-tumor necrosis factor (TNF)-alpha therapy with etanercept, a recombinant TNF receptor that binds to and functionally inactivates TNF-alpha, was shown to improve the functional status of patients with congestive heart failure (CHF). Because administration of TNF-alpha has been shown experimentally to depress endothelium-dependent relaxation, we hypothesized that TNF-alpha antagonism with etanercept might improve the depressed systemic endothelial vasodilator function, which importantly contributes to increased peripheral vascular resistance in patients with advanced CHF. METHODS AND RESULTS: Endothelium-dependent (acetylcholine, ACH; 10 to 50 microgram/min) and endothelium-independent (sodium nitroprusside, SNP; 2 to 8 microgram/min) forearm blood flow (FBF) responses were measured by venous occlusion plethysmography in 13 patients with documented CHF (New York Heart Association class III) before, 6 hours after, and 7 days after subcutaneous injection of a single dose of 25 mg etanercept. Maximum ACH-induced FBF increased significantly from 6.9+/-1.0 to 13.0+/-1.6 mL/min per 100 mL of forearm tissue (P<0.05) 6 hours after administration of etanercept and returned to 7.0+/-1.1 mL/min per 100 mL of forearm tissue after 7 days (P=NS), whereas SNP-induced FBF responses were not significantly affected. In contrast, FBF responses were not altered in control CHF patients, who did not receive etanercept (n=5). Etanercept-induced increases in ACH-mediated FBF were closely correlated with baseline TNF-alpha serum levels (r=0.66; P<0.02). CONCLUSIONS: The administration of etanercept profoundly improves systemic endothelial vasodilator capacity in patients with advanced heart failure, suggesting an important role of inflammatory mediators for impaired endothelial vasoreactivity in CHF. Improvement of systemic endothelial function might importantly contribute to the beneficial effects of etanercept on the functional status of patients with CHF.

Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response.

Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.